The actions of many hormones and neurotransmitters are mediated by the members of a superfamily of receptors coupled to heterotrimeric guanine nucleotide - binding proteins (G proteins). These receptors are characterized by a highly conserved topographical arrangement in which seven transmembrane domains are connected by intracellular and extracellular loops. The interaction between these receptors and G proteins is mediated in large part by the third intracellular loop of the receptor. Coexpression of the third intracellular loop of the [alpha.sub.1B]-adrenergic receptor with its parent receptor inhibited receptor-mediated activation of phospholipase C. The inhibition extended to the closely related [alpha.sub.c]-adrenergic receptor subtype, but not the phospholipase C - coupled M1 muscarinic acetylcholine receptor nor the adenylate cyclase - coupled [D.sub.1A] dopamine receptor. These results suggest that the receptor - G protein interface may represent a target for receptor antagonist drugs.